The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Thioredoxin-1(Trx-1)is a petite redox protein primarily encountered in mammalian cells.It responds to alterations in the redox environment by facilitating electron transfer and regulating associated proteins.This paper provides a concise overview of Trx-1,focusing on its altered expression patterns during cerebral ischemia.The emphasis is on its neuroprotective attributes following cerebral ischemia,encompassing anti-oxidation,anti-inflammation,anti-apoptosis,promotion of cell growth,angiogenesis,and its involvement in cerebral ischemia-related pathologies.

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

ObjectiveTo investigate the protective effect of Danggui Shaoyaosan （DSS）-contained serum on β-amyloid （Aβ）_1-40-injured rat adrenal pheochromocytoma PC12 cells and its mechanism in regulating ubiquitin-proteasome pathway （UPP）. MethodAβ_1-40 was used to intervene PC12 cells to prepare the cell models of Alzheimer's disease （AD）， and the experiment was divided into the blank， model， and DSS-contained serum high， medium， and low-dose groups （10%， 5%， and 2.5%）. Cell viability and apoptosis were detected using cell counting kit-8 （CCK-8） method and flow cytometry， respectively. The content of Aβ and p-Tau protein was determined by enzyme-linked immunosorbent assay （ELISA）. The ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase1 （UCHL1）， and UCHL3 protein expressions of UPP were displayed using immunofluorescence cytochemistry （ICC）， and the mRNA and protein expression levels of Ub， E3-parkin， 26S， UCHL1， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultThe data of the CCK8 experiment verified that 5 μmol·L^-1 and 48 hours were the optimal conditions for modeling Aβ_1-40-injured PC12 cells. As compared with the blank group， the cell viability rate in the model group decreased （P<0.05） with an increased apoptosis rate （P<0.05）， the content of Aβ and p-Tau contents was elevated （P<0.05）， the mRNA and protein expression levels of Ub increased， and the mRNA and protein expression levels of 26S， E3， and UCHL1+3 decreased （P<0.05）. As compared with the model group， the cell viability rate in the DSS-contained medium-dose group increased （P<0.05）， whereas the apoptosis rate in each DSS-contained group decreased （P<0.05）. The content of Aβ in each DDS-contained group decreased （P<0.05）， and the content of p-Tau in the DDS-contained high and medium-dose groups decreased （P<0.05）. The mRNA expression level of Ub decreased， and that of 26S increased in each DDS-contained group （P<0.05）. The mRNA expression level of UCHL1 in the DDS-contained medium-dose group increased （P<0.05）， and the mRNA expression levels of E3 and UCHL 3 in the DDS-contained high and medium-dose groups increased （P<0.05）. The protein expression level of Ub in each DDS-contained group decreased， and the protein expression levels of 26S， E3， and UCHL1+3 in the DDS high and medium-dose groups increased. The DSS-contained serum medium-dose group exerted the optimal effect. ConclusionDSS-contained serum can increase cell viability rate， reduce cell apoptosis rate， eliminate Aβ and p-Tau protein deposits， and exert protective effects on Aβ_1-40-injured PC12 cells. Its mechanism may involve UPP via decreasing the expression of Ub and increasing that of 26S， E3， UCHL1， and UCHL3.

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)₃ gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)₃ gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Objective To develope a deep learning algorithm for pathological classification of chronic gastritis and assess its performance using whole-slide images (WSIs). Methods We retrospectively collected 1,250 gastric biopsy specimens (1,128 gastritis, 122 normal mucosa) from PLA General Hospital. The deep learning algorithm based on DeepLab v3 (ResNet-50) architecture was trained and validated using 1,008 WSIs and 100 WSIs, respectively. The diagnostic performance of the algorithm was tested on an independent test set of 142 WSIs, with the pathologists' consensus diagnosis as the gold standard. Results The receiver operating characteristic (ROC) curves were generated for chronic superficial gastritis (CSuG), chronic active gastritis (CAcG), and chronic atrophic gastritis (CAtG) in the test set, respectively.The areas under the ROC curves (AUCs) of the algorithm for CSuG, CAcG, and CAtG were 0.882, 0.905 and 0.910, respectively. The sensitivity and specificity of the deep learning algorithm for the classification of CSuG, CAcG, and CAtG were 0.790 and 1.000 (accuracy 0.880), 0.985 and 0.829 (accuracy 0.901), 0.952 and 0.992 (accuracy 0.986), respectively. The overall predicted accuracy for three different types of gastritis was 0.867. By flagging the suspicious regions identified by the algorithm in WSI, a more transparent and interpretable diagnosis can be generated. Conclusion The deep learning algorithm achieved high accuracy for chronic gastritis classification using WSIs. By pre-highlighting the different gastritis regions, it might be used as an auxiliary diagnostic tool to improve the work efficiency of pathologists.
Algorithms ; Deep Learning ; Gastritis/diagnosis* ; Humans ; ROC Curve ; Retrospective Studies

Aim To investigate the role of Nampt in regulating ERK1/2 in cardiac hypertrophy and its mechanisms. Methods The primary neonatal rat cardiomyocytes were stimulated by phenylephrine (PE) (100 μmol · L

OBJECTIVE: To detect the relationship between CTGF in the bone marrow of MM patients and osteolytic lesion of myeloma, moreover, to investigate the clinical significance of CTGF in MM. METHODS: Fifity-four MM patients treated in our hospital from March 2019 to April 2020 were enrolled, and 28 healthy volunteers were selected as the control group. The plasma in bone marrow of the patients was collected, and the ELISA was used to detect the level of CTGF in bone marrow plasma and the relationship between its and clinical characteristics were statistically analyzed. RESULTS: The CTGF level of MM patients was significantly higher than those in the healthy control group (P<0.001); the CTGF level in male patients was higher than that in female patients (P=0.007); the CTGF level in MM patients with osteolytic lesions was significantly higher than patients without osteolytic lesions and controls (P=0.007, P=0.001). The CTGF level in MM patients was positively correlated with the number of bone lesions (P<0.001, r=0.52). CTGF levels in patients with ≥3 bone lesions were significantly higher than those with <3 bone lesions and without bone lesions (P=0.014, P=0.002). ROC curve result showed that CTGF expression level shows a significant diagnostic value for MM bone disease (P<0.001). CONCLUSION The abnormally high expression of CTGF level in MM patients is related to the degree of myelomas osteolytic lesions and can reflect the progress of MM.
Bone Marrow ; Connective Tissue Growth Factor ; Female ; Humans ; Male ; Multiple Myeloma ; Osteolysis ; Patients ; ROC Curve

Anti-Arrhythmia Agents ; Brugada Syndrome/complications* ; Bundle-Branch Block/complications* ; Electrocardiography ; Humans ; Quinidine ; Ventricular Fibrillation

Embolism, Air ; etiology ; Humans ; Intraoperative Complications ; Resuscitation ; Vitrectomy ; adverse effects